NO313287B1 - Fremgangsmåter for fremstilling av HIV-protease inhibitorer - Google Patents

Fremgangsmåter for fremstilling av HIV-protease inhibitorer Download PDF

Info

Publication number: NO313287B1
Authority: NO; Norway
Prior art keywords: group; formula; compound; alkyl; aryl
Prior art date: 1996-09-05

Application number

NO19991072A

Other languages

English (en)

Norwegian (no)

Other versions

NO991072D0 (no

NO991072L (no

Inventor

Kathleen R Whitten

Michael E Deason

Original Assignee

Japan Tobacco Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-09-05

Filing date

1999-03-04

Publication date

2002-09-09

1999-03-04 Application filed by Japan Tobacco Inc filed Critical Japan Tobacco Inc

1999-03-04 Publication of NO991072D0 publication Critical patent/NO991072D0/no

1999-03-04 Publication of NO991072L publication Critical patent/NO991072L/no

2002-09-09 Publication of NO313287B1 publication Critical patent/NO313287B1/no

Links

238000000034 method Methods 0.000 title claims description 55
239000004030 hiv protease inhibitor Substances 0.000 title description 11
150000001875 compounds Chemical class 0.000 claims description 132
125000000217 alkyl group Chemical group 0.000 claims description 91
125000003118 aryl group Chemical group 0.000 claims description 76
125000001072 heteroaryl group Chemical group 0.000 claims description 50
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 43
238000006243 chemical reaction Methods 0.000 claims description 41
125000000753 cycloalkyl group Chemical group 0.000 claims description 41
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 38
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 34
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 33
239000002904 solvent Substances 0.000 claims description 26
239000007787 solid Substances 0.000 claims description 23
238000002360 preparation method Methods 0.000 claims description 20
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 16
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
229910052760 oxygen Inorganic materials 0.000 claims description 15
239000001301 oxygen Substances 0.000 claims description 15
239000012296 anti-solvent Substances 0.000 claims description 14
125000003710 aryl alkyl group Chemical group 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 14
150000002367 halogens Chemical class 0.000 claims description 14
230000008569 process Effects 0.000 claims description 14
125000002577 pseudohalo group Chemical group 0.000 claims description 14
238000003756 stirring Methods 0.000 claims description 14
125000005842 heteroatom Chemical group 0.000 claims description 13
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
239000003960 organic solvent Substances 0.000 claims description 9
229940098779 methanesulfonic acid Drugs 0.000 claims description 8
238000010511 deprotection reaction Methods 0.000 claims description 6
238000001035 drying Methods 0.000 claims description 6
238000001914 filtration Methods 0.000 claims description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
238000001694 spray drying Methods 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 3
239000007791 liquid phase Substances 0.000 claims description 2
239000007790 solid phase Substances 0.000 claims description 2
238000005406 washing Methods 0.000 claims description 2
-1 hydroxybenzotriazole ester Chemical class 0.000 description 66
239000000203 mixture Substances 0.000 description 61
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 32
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
239000002585 base Substances 0.000 description 27
239000012458 free base Substances 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
239000000243 solution Substances 0.000 description 25
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
239000002253 acid Substances 0.000 description 24
QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 23
229960000884 nelfinavir Drugs 0.000 description 23
QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
NQHXCOAXSHGTIA-SKXNDZRYSA-N nelfinavir mesylate Chemical compound CS(O)(=O)=O.CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 NQHXCOAXSHGTIA-SKXNDZRYSA-N 0.000 description 18
229960005230 nelfinavir mesylate Drugs 0.000 description 18
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
239000000047 product Substances 0.000 description 14
239000002002 slurry Substances 0.000 description 14
125000004432 carbon atom Chemical group C* 0.000 description 13
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
150000001412 amines Chemical class 0.000 description 12
238000004519 manufacturing process Methods 0.000 description 12
238000010992 reflux Methods 0.000 description 12
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 11
150000002148 esters Chemical group 0.000 description 11
235000011121 sodium hydroxide Nutrition 0.000 description 11
COLDUSGLGQXXEJ-UHFFFAOYSA-N (3-carbonochloridoyl-2-methylphenyl) acetate Chemical compound CC(=O)OC1=CC=CC(C(Cl)=O)=C1C COLDUSGLGQXXEJ-UHFFFAOYSA-N 0.000 description 10
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
238000004128 high performance liquid chromatography Methods 0.000 description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 8
125000003282 alkyl amino group Chemical group 0.000 description 8
239000012065 filter cake Substances 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
150000003839 salts Chemical class 0.000 description 8
RIERSGULWXEJKL-UHFFFAOYSA-N 3-hydroxy-2-methylbenzoic acid Chemical class CC1=C(O)C=CC=C1C(O)=O RIERSGULWXEJKL-UHFFFAOYSA-N 0.000 description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
125000002252 acyl group Chemical group 0.000 description 7
150000001409 amidines Chemical class 0.000 description 7
229940125898 compound 5 Drugs 0.000 description 7
125000005843 halogen group Chemical group 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
LHVJUPHCLWIPLZ-UHFFFAOYSA-N 3-acetyloxy-2-methylbenzoic acid Chemical compound CC(=O)OC1=CC=CC(C(O)=O)=C1C LHVJUPHCLWIPLZ-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
125000004453 alkoxycarbonyl group Chemical group 0.000 description 6
125000005115 alkyl carbamoyl group Chemical group 0.000 description 6
150000004649 carbonic acid derivatives Chemical class 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
150000007529 inorganic bases Chemical class 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
125000002950 monocyclic group Chemical group 0.000 description 6
150000007530 organic bases Chemical class 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
239000007921 spray Substances 0.000 description 6
125000001424 substituent group Chemical group 0.000 description 6
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 6
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 5
239000012973 diazabicyclooctane Substances 0.000 description 5
150000002170 ethers Chemical class 0.000 description 5
150000004820 halides Chemical class 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
229910000000 metal hydroxide Inorganic materials 0.000 description 5
150000004692 metal hydroxides Chemical class 0.000 description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
239000008213 purified water Substances 0.000 description 5
125000000547 substituted alkyl group Chemical group 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
229910004373 HOAc Inorganic materials 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
125000002619 bicyclic group Chemical group 0.000 description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
230000008878 coupling Effects 0.000 description 4
238000010168 coupling process Methods 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 4
125000001033 ether group Chemical group 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 4
150000002825 nitriles Chemical class 0.000 description 4
239000003495 polar organic solvent Substances 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
125000005270 trialkylamine group Chemical group 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical class CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 3
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
230000001476 alcoholic effect Effects 0.000 description 3
239000003513 alkali Substances 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
125000004414 alkyl thio group Chemical group 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
150000001555 benzenes Chemical class 0.000 description 3
235000019445 benzyl alcohol Nutrition 0.000 description 3
150000001735 carboxylic acids Chemical class 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 3
125000000623 heterocyclic group Chemical group 0.000 description 3
229910052739 hydrogen Inorganic materials 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 3
229940011051 isopropyl acetate Drugs 0.000 description 3
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 3
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical class C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 3
125000004076 pyridyl group Chemical group 0.000 description 3
125000006413 ring segment Chemical group 0.000 description 3
239000011734 sodium Substances 0.000 description 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
229940122440 HIV protease inhibitor Drugs 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
239000002841 Lewis acid Substances 0.000 description 2
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
239000005864 Sulphur Chemical group 0.000 description 2
241000700605 Viruses Species 0.000 description 2
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 2
150000001336 alkenes Chemical class 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
238000013459 approach Methods 0.000 description 2
239000011260 aqueous acid Substances 0.000 description 2
238000000889 atomisation Methods 0.000 description 2
150000001540 azides Chemical class 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
150000008422 chlorobenzenes Chemical class 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
238000004821 distillation Methods 0.000 description 2
238000009826 distribution Methods 0.000 description 2
150000002118 epoxides Chemical class 0.000 description 2
230000032050 esterification Effects 0.000 description 2
238000005886 esterification reaction Methods 0.000 description 2
125000005670 ethenylalkyl group Chemical group 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000007789 gas Substances 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
239000008240 homogeneous mixture Substances 0.000 description 2
150000002430 hydrocarbons Chemical group 0.000 description 2
238000007327 hydrogenolysis reaction Methods 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
239000012535 impurity Substances 0.000 description 2
239000012948 isocyanate Substances 0.000 description 2
150000002513 isocyanates Chemical class 0.000 description 2
125000001786 isothiazolyl group Chemical group 0.000 description 2
150000002540 isothiocyanates Chemical class 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
239000007788 liquid Substances 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
229910017604 nitric acid Inorganic materials 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
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230000035755 proliferation Effects 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
229910052705 radium Inorganic materials 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
229910052701 rubidium Inorganic materials 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
229950009390 symclosene Drugs 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
KBMBVTRWEAAZEY-UHFFFAOYSA-N trisulfane Chemical compound SSS KBMBVTRWEAAZEY-UHFFFAOYSA-N 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/287—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/12—Acetic acid esters
- C07C69/14—Acetic acid esters of monohydroxylic compounds
- C07C69/145—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols
- C07C69/157—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols containing six-membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/62—Halogen-containing esters
- C07C69/63—Halogen-containing esters of saturated acids
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Virology (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Molecular Biology (AREA)
Tropical Medicine & Parasitology (AREA)
AIDS & HIV (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Peptides Or Proteins (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

NO19991072A 1996-09-05 1999-03-04 Fremgangsmåter for fremstilling av HIV-protease inhibitorer NO313287B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US70841196A	1996-09-05	1996-09-05
PCT/US1997/015468 WO1998009951A2 (en)	1996-09-05	1997-09-04	Intermediates for making hiv-protease inhibitors and methods of making hiv-protease inhibitors

Publications (3)

Publication Number	Publication Date
NO991072D0 NO991072D0 (no)	1999-03-04
NO991072L NO991072L (no)	1999-03-04
NO313287B1 true NO313287B1 (no)	2002-09-09

Family

ID=24845703

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19991072A NO313287B1 (no)	1996-09-05	1999-03-04	Fremgangsmåter for fremstilling av HIV-protease inhibitorer

Country Status (32)

Country	Link
EP (2)	EP0927165B1 (de)
JP (3)	JP4149000B2 (de)
KR (1)	KR100563289B1 (de)
CN (2)	CN1305854C (de)
AP (2)	AP1322A (de)
AT (2)	ATE309990T1 (de)
AU (2)	AU740369B2 (de)
BG (2)	BG64793B1 (de)
BR (1)	BR9713192A (de)
CA (1)	CA2264756A1 (de)
CZ (2)	CZ298175B6 (de)
DE (2)	DE69726298T2 (de)
DK (2)	DK0927165T3 (de)
EA (1)	EA002051B1 (de)
EE (1)	EE04465B1 (de)
ES (2)	ES2252586T3 (de)
GE (1)	GEP20022799B (de)
HU (1)	HUP0000028A3 (de)
IL (1)	IL128567A (de)
IS (1)	IS2030B (de)
NO (1)	NO313287B1 (de)
NZ (1)	NZ334909A (de)
OA (1)	OA10988A (de)
PL (2)	PL201758B1 (de)
PT (1)	PT927165E (de)
SG (1)	SG94780A1 (de)
SI (2)	SI1361216T1 (de)
SK (2)	SK284899B6 (de)
TR (1)	TR199900473T2 (de)
UA (1)	UA67727C2 (de)
WO (1)	WO1998009951A2 (de)
YU (1)	YU11599A (de)

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH0641038A (ja) *	1992-07-17	1994-02-15	Mitsubishi Kasei Corp	カルボン酸誘導体
US5484926A (en) *	1993-10-07	1996-01-16	Agouron Pharmaceuticals, Inc.	HIV protease inhibitors
JPH07248183A (ja) *	1994-03-11	1995-09-26	Osaka Gas Co Ltd	浴室兼用衣類乾燥室
JP3298293B2 (ja) *	1994-03-14	2002-07-02	松下電器産業株式会社	厨芥処理機
AU4953796A (en) *	1995-03-15	1996-10-02	Sanyko Company, Limited	Dipeptide compounds having ahpba structure
WO1997011937A1 (en) *	1995-09-26	1997-04-03	Japan Tobacco Inc.	Process for producing amide derivatives and intermediates
US5962704A (en) *	1995-09-26	1999-10-05	Japan Tobacco Inc.	Production of amide derivatives and intermediate compounds therefor
US6121468A (en) *	1995-09-26	2000-09-19	Japan Tobacco Inc.	Process for producing amide derivatives and intermediate compounds
CZ230398A3 (cs) *	1996-02-24	1999-01-13	Basf Aktiengesellschaft	Derivát pyrazol-4-ylhetaroylu, způsob jeho přípravy a herbicidní prostředek, který ho obsahuje

1997
- 1997-04-09 UA UA99041906A patent/UA67727C2/uk unknown
- 1997-09-04 GE GEAP19974736A patent/GEP20022799B/en unknown
- 1997-09-04 HU HU0000028A patent/HUP0000028A3/hu unknown
- 1997-09-04 AP APAP/P/1999/001497A patent/AP1322A/en active
- 1997-09-04 EP EP97941402A patent/EP0927165B1/de not_active Expired - Lifetime
- 1997-09-04 SI SI9730719T patent/SI1361216T1/sl unknown
- 1997-09-04 SK SK282-99A patent/SK284899B6/sk not_active IP Right Cessation
- 1997-09-04 AT AT03013275T patent/ATE309990T1/de not_active IP Right Cessation
- 1997-09-04 PL PL381445A patent/PL201758B1/pl not_active IP Right Cessation
- 1997-09-04 PT PT97941402T patent/PT927165E/pt unknown
- 1997-09-04 DE DE69726298T patent/DE69726298T2/de not_active Expired - Fee Related
- 1997-09-04 SI SI9730605T patent/SI0927165T1/xx unknown
- 1997-09-04 CN CNB2004100073691A patent/CN1305854C/zh not_active Expired - Fee Related
- 1997-09-04 DK DK97941402T patent/DK0927165T3/da active
- 1997-09-04 CZ CZ20070084A patent/CZ298175B6/cs not_active IP Right Cessation
- 1997-09-04 DE DE69734689T patent/DE69734689T2/de not_active Expired - Fee Related
- 1997-09-04 BR BR9713192-0A patent/BR9713192A/pt not_active Application Discontinuation
- 1997-09-04 AU AU43317/97A patent/AU740369B2/en not_active Ceased
- 1997-09-04 IL IL12856797A patent/IL128567A/en not_active IP Right Cessation
- 1997-09-04 ES ES03013275T patent/ES2252586T3/es not_active Expired - Lifetime
- 1997-09-04 AT AT97941402T patent/ATE254603T1/de not_active IP Right Cessation
- 1997-09-04 SK SK90-2005A patent/SK285278B6/sk not_active IP Right Cessation
- 1997-09-04 SG SG200101308A patent/SG94780A1/en unknown
- 1997-09-04 YU YU11599A patent/YU11599A/sh unknown
- 1997-09-04 NZ NZ334909A patent/NZ334909A/en unknown
- 1997-09-04 CZ CZ0071699A patent/CZ298174B6/cs not_active IP Right Cessation
- 1997-09-04 CN CNB971984484A patent/CN1183117C/zh not_active Expired - Fee Related
- 1997-09-04 EP EP03013275A patent/EP1361216B1/de not_active Expired - Lifetime
- 1997-09-04 CA CA002264756A patent/CA2264756A1/en not_active Abandoned
- 1997-09-04 ES ES97941402T patent/ES2210573T3/es not_active Expired - Lifetime
- 1997-09-04 AP APAP/P/2003/002938A patent/AP2003002938A0/en unknown
- 1997-09-04 JP JP51283198A patent/JP4149000B2/ja not_active Expired - Fee Related
- 1997-09-04 EE EEP199900109A patent/EE04465B1/xx not_active IP Right Cessation
- 1997-09-04 WO PCT/US1997/015468 patent/WO1998009951A2/en not_active Ceased
- 1997-09-04 TR TR1999/00473T patent/TR199900473T2/xx unknown
- 1997-09-04 DK DK03013275T patent/DK1361216T3/da active
- 1997-09-04 KR KR1019997001902A patent/KR100563289B1/ko not_active Expired - Fee Related
- 1997-09-04 EA EA199900257A patent/EA002051B1/ru not_active IP Right Cessation
- 1997-09-04 PL PL331801A patent/PL198408B1/pl not_active IP Right Cessation
1999
- 1999-02-19 IS IS4982A patent/IS2030B/is unknown
- 1999-03-03 OA OA9900049A patent/OA10988A/en unknown
- 1999-03-04 NO NO19991072A patent/NO313287B1/no not_active IP Right Cessation
- 1999-04-02 BG BG103305A patent/BG64793B1/bg unknown
2002
- 2002-01-31 AU AU14736/02A patent/AU766155B2/en not_active Ceased
2006
- 2006-01-18 BG BG109411A patent/BG65237B1/bg unknown
2007
- 2007-10-29 JP JP2007280975A patent/JP2008088178A/ja active Pending
- 2007-10-29 JP JP2007280974A patent/JP2008056693A/ja not_active Withdrawn

Also Published As

Publication number	Publication date
DE69726298D1 (de)	2003-12-24
NO991072D0 (no)	1999-03-04
DE69734689T2 (de)	2006-06-08
BG64793B1 (bg)	2006-04-28
JP4149000B2 (ja)	2008-09-10
CN1537846A (zh)	2004-10-20
AU766155B2 (en)	2003-10-09
BG103305A (en)	2000-01-31
PT927165E (pt)	2004-04-30
SK28299A3 (en)	1999-11-08
YU11599A (sh)	2000-03-21
DK1361216T3 (da)	2006-01-23
CA2264756A1 (en)	1998-03-12
CZ298175B6 (cs)	2007-07-11
OA10988A (en)	2001-11-01
EP0927165B1 (de)	2003-11-19
PL331801A1 (en)	1999-08-02
EA199900257A1 (ru)	1999-08-26
KR100563289B1 (ko)	2006-03-22
EE04465B1 (et)	2005-04-15
JP2008088178A (ja)	2008-04-17
DE69734689D1 (de)	2005-12-22
DE69726298T2 (de)	2004-05-27
ES2252586T3 (es)	2006-05-16
WO1998009951A2 (en)	1998-03-12
DK0927165T3 (da)	2004-03-15
AU4331797A (en)	1998-03-26
IL128567A (en)	2004-03-28
EA002051B1 (ru)	2001-12-24
KR20010029489A (ko)	2001-04-06
IS2030B (is)	2005-08-15
PL198408B1 (pl)	2008-06-30
EP1361216B1 (de)	2005-11-16
NZ334909A (en)	2000-06-23
HUP0000028A3 (en)	2003-05-28
AU1473602A (en)	2002-03-14
SI1361216T1 (sl)	2006-02-28
AP9901497A0 (en)	1999-06-30
HK1062171A1 (en)	2004-10-21
ATE254603T1 (de)	2003-12-15
TR199900473T2 (xx)	1999-06-21
HUP0000028A2 (hu)	2000-05-28
WO1998009951A3 (en)	1998-07-09
CN1305854C (zh)	2007-03-21
EP1361216A1 (de)	2003-11-12
ES2210573T3 (es)	2004-07-01
JP2008056693A (ja)	2008-03-13
ATE309990T1 (de)	2005-12-15
SK285278B6 (sk)	2006-10-05
CN1232455A (zh)	1999-10-20
EE9900109A (et)	1999-12-15
JP2001500495A (ja)	2001-01-16
SK284899B6 (sk)	2006-02-02
AP2003002938A0 (en)	2003-12-31
SG94780A1 (en)	2003-03-18
BG65237B1 (bg)	2007-09-28
GEP20022799B (en)	2002-09-25
AP1322A (en)	2004-11-04
PL201758B1 (pl)	2009-05-29
SI0927165T1 (en)	2004-04-30
CN1183117C (zh)	2005-01-05
NO991072L (no)	1999-03-04
AU740369B2 (en)	2001-11-01
IL128567A0 (en)	2000-01-31
CZ298174B6 (cs)	2007-07-11
CZ71699A3 (cs)	1999-06-16
EP0927165A2 (de)	1999-07-07
UA67727C2 (uk)	2004-07-15
BR9713192A (pt)	1999-12-21
IS4982A (is)	1999-02-19

Legal Events

Date	Code	Title	Description
2010-04-26	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
DK158980B (da)	1990-08-13	Analogifremgangsmaade til fremstilling af 2,5-bis-(2,2,2-trifluorethoxy)-n-(2-piperidylmethyl)benzamid eller et farmaceutisk acceptabelt syreadditionssalt deraf
DK154555B (da)	1988-11-28	Analogifremgangsmaade til fremstilling af carbazolyl-(4)-oxy-propanolaminderivater eller deres farmakologisk anvendelige salte
JPS6058750B2 (ja)	1985-12-21	Ｎ−（１−ベンジルピロリジニル−２−メチル）置換ベンズアミド誘導体またはその塩類の製造法
RU2137769C1 (ru)	1999-09-20	Способ получения эпоксида
US6512135B2 (en)	2003-01-28	Intermediates for making HIV-protease inhibitors and methods for making HIV-protease inhibitors
CA2264725A1 (en)	1998-03-12	Methods of making hiv-protease inhibitors and intermediates for making them
US7078543B2 (en)	2006-07-18	Methods for producing oxirane carboxylic acids and derivatives thereof
AU740369B2 (en)	2001-11-01	Intermediates for making HIV-protease inhibitors and methods of making HIV-protease inhibitors
KR900004144B1 (ko)	1990-06-16	1,2,5,6-테트라히드로-4H-피롤로[3,2,1-ij]퀴놀린-4-온의 제조방법
US2459111A (en)	1949-01-11	Pantoyltauramides and preparation of the same
JP4788049B2 (ja)	2011-10-05	ジカルボン酸ジエステル誘導体およびその製造方法
MXPA99002152A (en)	2000-11-01	Intermediates for making hiv-protease inhibitors and methods of making hiv-protease inhibitors
SU1124885A3 (ru)	1984-11-15	Способ получени производных дихлорацетилированного вторичного амида
KR800001133B1 (ko)	1980-10-12	복소환 치환기를 가진 5-설파모일벤조산 유도체의 제조방법
JPH0583537B2 (de)	1993-11-26
DUMITRAŞCU et al.	2002	Synthesis and NMR study of 2-[N-(aryl) carbamoylmethyl] phthalazinium iodides
JPH02300154A (ja)	1990-12-12	安息香酸誘導体の製造法